Department of Microbiology

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Faculty Profile

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Akira Kaji, Ph.D.

Professor of Microbiology
Department: Microbiology

Contact information
135B Anatomy-Chemistry Bldg
Philadelphia, PA 19104-6076
Office: 215-898-8828
Fax: 215-573-2221
B.S. (Faculty of Pharmaceutical Sciences)
University of Tokyo, 1953.
Johns Hopkins University, McCollum Pratt Institute (Dr.W. D. McElroy), 1958.
Permanent link
> Perelman School of Medicine   > Faculty   > Details

Description of Research Expertise

We study protein synthesis. Protein synthesis consists of four steps; initiation, elongation, termination and recycling of ribosomes for new round of translation. In 1970, we discovered the recycling step and continue to work on this step. In prokaryotes, this step is catalyzed by two soluble factors, ribosome recycling factor (RRF) and elongation factor G (EF-G). Our lab discovered RRF (an essential protein for maintenance of bacterial life), and the gene for RRF (frr) (for review see (1,2). RRF is essential for maintenance of mitochondria in eukaryotes. Our recent work elucidated the structural aspects of the mechanism of the action of RRF at the atomic level (3,4). GTP energy is constantly required to keep the subunits separated under physiological ionic conditions (5). We have recently shown that RRF, together with other factors is involved in the rescue of the stalled ribosomes (6).
We have recently extended our work on the ribosome recycling step to eukaryotes. In yeast, there is no RRF homologue in cytoplasm and nothing was known about the ribosome recycling step. In 2010, we showed that eEF3 and ATP disassemble, and hence recycle, the yeast post-termination complexes (PoTC) (7). eEF3 was already known to be essential for peptide chain elongation in yeast but we found the second important function of this factor the ribosome recycling. We recently found that the order of events in the yeast recycling is that tRNA release, mRNA release and ribosome splitting (8).

The following is a short review of our past work. In 1963, we have discovered that specific tRNA binds to the complex of mRNA and ribosome. This finding was essential to decipher the genetic code (9). Regarding RRF, upon in vivo inactivation of RRF, the ribosome starts the unscheduled translation downstream from the termination codon. Crystal structure by X-ray crystallography as well as solution structure by NMR has revealed that RRF is a near perfect structural mimic of tRNA. Indeed, we found that RRF functionally mimics tRNA in that it moves in the inter-subunits space like tRNA does. However, the mode of RRF binding to the ribosome is different from that of tRNA. We also discovered arginyl-tRNA protein transferase in 1963(10). This enzyme is an essential for higher eukaryotes and involved in post-translational protein modification (11)

1. Janosi, L., Hara, H., Zhang, S., and Kaji, A. (1996) Advances in biophysics 32, 121-201
2. Hirokawa, G., Demeshkina, N., Iwakura, N., Kaji, H., and Kaji, A. (2006) Trends in biochemical sciences 31, 143-149
3. Yokoyama, T., Shaikh, T. R., Iwakura, N., Kaji, H., Kaji, A., and Agrawal, R. K. (2012) EMBO J 31, 1836-1846
4. Pai, R. D., Zhang, W., Schuwirth, B. S., Hirokawa, G., Kaji, H., Kaji, A., and Cate, J. H. (2008) J Mol Biol 376, 1334-1347
5. Hirokawa, G., Iwakura, N., Kaji, A., and Kaji, H. (2008) Nucleic acids research 36, 6676-6687
6. Vivanco-Dominguez, S., Bueno-Martinez, J., Leon-Avila, G., Iwakura, N., Kaji, A., Kaji, H., and Guarneros, G. (2012) J Mol Biol 417, 425-439
7. Kurata, S., Nielsen, K. H., Mitchell, S. F., Lorsch, J. R., Kaji, A., and Kaji, H. (2010) Proceedings of the National Academy of Sciences of the United States of America 107, 10854-10859
8. Kurata, S., Shen, B., Liu, J. O., Takeuchi, N., Kaji, A., and Kaji, H. (2013) Nucleic acids research 41, 264-276
9. Kaji, A., and Kaji, H. (2005) The History of Deciphering the Genetic Code: Setting the Record Straight. in The Inside Story: DNA to RNA to Protein (Witkowski, J. A. ed.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. pp 209
10. Kaji, H., Novelli, G. D., and Kaji, A. (1963) Biochimica et biophysica acta 76, 474-477
11. Kwon, Y. T., Kashina, A. S., Davydov, I. V., Hu, R. G., An, J. Y., Seo, J. W., Du, F., and Varshavsky, A. (2002) Science 297, 96-99

Selected Publications

Go Hirokawa, Hachiro Inokuchi, Hideko Kaji, Kazuei Igarashi and Akira Kaji: In vivo effect of inactivation of ribosome recycling factor ---Fate of ribosomes after unscheduled translation downstream of open reading frame. Mol Microbiol 54: 1011-1021, 2004.

Moll, I., Hirokawa, G., Kiel, M. C., Kaji, A., and Blasi, U. : Translation initiation with 70S ribosomes: an alternative pathway for leaderless mRNAs. Nucleic Acids Res 32: 3354-3363, 2004.

Agrawal, R. K., Sharma, M. R., Kiel, M. C., Hirokawa, G., Booth, T. M., Spahn, C. M. T., Grassucci, R. A., Kaji, A., and Frank, J. : Visualization of ribosome-recycling factor on the Escherichia coli 70S ribosome: Functional implications. PNAS 101: 8900-05, 2004.

Kiel, M. C., Raj, V. S., Kaji, H., Kaji, A.: Release of ribosome-bound ribosome recycling factor by elongation factor G. J Biol Chem 278: 48041-50, 2003.

Teyssier,E., Hirokawa,G., Tretiakova,A., Jameson,B., Kaji,A., and Kaji, H.: Temperature sensitive mutation in yeast mitochondrial ribosome recycling factor (RRF). Nucleic Acid Research 31: 4218-26, 2003.

Yoshida T., Uchiyama S., Nakano H., Kashimori H., Kijima H., Ohshima T., Saihara Y., Ishino T., Shimahara H., Yoshida T., Yokose K., Ohkubo T., Kaji A., Kobayashi Y.: Solution structure of the ribosome recycling factor from Aquifex aeolicus. Biochemistry 40(8): 2387-96, Feb 27 2001.

Hirokawa, G., Muto, A., Kiel, M. and Kaji, A: The Fourth Step of Protein synthesis: Disassembly of Post Termination Complex. The 3rd International Symposium on Ribosome Engineering, at Tsukuba, Japan. Invited speaker, 45 minutes talk Jan. 2001.

Akira Kaji, Michael Kiel, Aiko Muto, Go Hirokawa and Hideko Kaji: The fourth step of protein biosynthesis catalyzed by ribosome recycling factor, RRF: An ideal target for new antimicrobial agents. 121st National Meeting of Japanese Pharmaceutical Society, Invited speaker for plenary lecture 1, 29A 153: 75, March 2001.

Atarashi K., Kaji A.: Inhibitory effect of heterologous ribosome recycling factor on growth of Escherichia coli. Journal of Bacteriology 182(21): 6154-60, Nov 2000.

Inokuchi Y., Hirashima A., Sekine Y., Janosi L., Kaji A.: Role of ribosome recycling factor (RRF) in translational coupling. EMBO Journal 19(14): 3788-98, Jul 17 2000.

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Last updated: 08/07/2015
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